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Contraception. Author manuscript; available in PMC 2013 September 01.

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Published in final edited form as:

Contraception. 2012 September ; 86(3): 199203. doi:10.1016/j.contraception.2012.01.008.

Contraindications to progestin-only oral contraceptive pills

among reproductive aged women
Kari White1, Joseph E. Potter2, Kristine Hopkins2, Leticia Fernndez3, Jon Amastae4, and
Daniel Grossman5,*
1Health Care Organization & Policy, University of Alabama at Birmingham, Birmingham, AL
35294
2Population

Research Center, University of Texas at Austin, Austin, TX 78712

3Department

of Family Medicine, University of Pretoria, Pretoria, South Africa 0084

4College

of Health Sciences and Department of Languages and Linguistics, University of Texas

at El Paso, El Paso, TX 79968

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5Ibis

Reproductive Health, Oakland, CA 94612

Abstract
BackgroundProgestin-only oral contraceptive pills (POPs) have fewer contraindications to
use compared to combined pills. However, the overall prevalence of contraindications to POPs
among reproductive aged women has not been assessed.
Study DesignWe collected information on contraindications to POPs in two studies: 1) the
Self-Screening Study, a sample of 1,267 reproductive aged women in the general population in El
Paso, Texas, and 2) the Prospective Study of Oral Contraceptive (OC) Users, a sample of current
OC users who obtained their pills in El Paso clinics (n=532) or over the counter (OTC) in Mexican
pharmacies (n=514). In the Self-Screening Study, we also compared womens self-assessment of
contraindications using a checklist to a clinicians evaluation.

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ResultsOnly 1.6% of women in the Self-Screening Study were identified as having at least one
contraindication to POPs. The sensitivity of the checklist for identifying women with at least one
contraindication was 75.0% (95% CI: 50.690.4%), and the specificity was 99.4% (95% CI: 98.8
99.7%). In total, 0.6% of women in the Prospective Study of OC Users reported having any
contraindication to POPs. There were no significant differences between clinic and OTC users.
ConclusionThe prevalence of contraindications to POPs was very low in these samples. POPs
may be the best choice for the first OTC oral contraceptive in the US.
Keywords
oral contraceptives; contraindications; self-screening; over-the-counter status

2012 Elsevier Inc. All rights reserved.

*

Corresponding author: Daniel Grossman, Ibis Reproductive Health, 1330 Broadway, Ste 1100, Oakland, CA 94612, Phone: (510)
986-8941, Fax: (510) 986-8960, DGrossman@ibisreproductivehealth.org.
Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our
customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of
the resulting proof before it is published in its final citable form. Please note that during the production process errors may be
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1. Introduction
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Oral contraceptive pills (OCs) are the most common method of contraception in the United
States (US) [1]. Although the relative safety of this method has been well-established and
some have advocated for making OCs available over-the-counter (OTC) [2,3], women
interested in starting or continuing with this method must still obtain a prescription from a
health care provider in the US. One of the justifications for maintaining the prescriptiononly status is that, during their clinician visit, women are screened for health conditions such
as hypertension and diabetes, which may increase their risk of myocardial infarction, stroke
or other complications while taking OCs [4]. However, these rare complications are
associated with the use of combined oral contraceptives (COCs) and not progestin-only pills
(POPs) [5].
According to the US Medical Eligibility Criteria (MEC), many more conditions are
considered relative (category 3) and absolute (category 4) contraindications to COCs
compared to POPs [6]. For example, hypertension, migraine headache with aura, and
smoking among women age 35 years and older conditions with the highest prevalence in
studies of reproductive aged women are not considered contraindications to POPs [69].

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In addition, conditions that are contraindications to POPs, such as past or current breast
cancer, cirrhosis, and use of anticonvulsants, have been found to be relatively uncommon in
several studies examining the prevalence of OC contraindications among reproductive aged
women in the US. Using data from the National Health and Nutrition Examination Survey
(NHANES), Shortridge and Miller [7] found that less than 2% of women reported having
breast, cervical or uterine cancer or current liver disease. Although some contraindications
were broadly defined in this study and data on others were not available in the NHANES,
several other studies also found that the prevalence of individual contraindicated conditions
was low - less than 1% among both women in the general population and women seeking
reproductive health services [810]. However, none of these studies reported on the overall
prevalence of having any POP contraindication.

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There is growing evidence that women can accurately screen themselves for most health
conditions that would contraindicate them for OC use. For example, women attending
family planning clinics in Washington completed a self-assessment of 20 health conditions
that would pose a risk to OC use, and the accuracy of this assessment was then compared to
their providers separate evaluation of these same conditions [10]. Patient-provider
agreement was 90% on 17 of these items. In another study conducted in Texas, researchers
also found a high level of agreement between contraindications identified through providers
assessment and those women reported in a self-administered checklist [8]. Disagreement
between women and providers on eligibility for OC use was largely due to misclassification
of migraine headaches and unrecognized hypertension, conditions that would not impact
womens eligibility for POP use.
The purpose of this analysis was to provide a more focused examination of the prevalence of
contraindications to POPs. Specifically, we assess the prevalence of individual POP
contraindications as well as the overall prevalence of having any POP contraindication in a
convenience sample of reproductive aged women and in a sample of current OC users
including those who have the option to obtain OCs over-the-counter in a counter in a reallife setting. We also examine how well womens self-assessment of these contraindications
compares to that of a health care provider.

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2. Materials and methods

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For this analysis, we use data from the Border Contraceptive Access Study (BCAS), which
examined OC use along the US-Mexico border. The study design, sample size justification
and characteristics of women participating in the two sub-studies of BCAS have been
published previously [8,9,11]; we briefly describe the relevant methods here. In the first
BCAS sub-study (the Self-Screening Study), bilingual (English/Spanish) female
interviewers recruited a convenience sample of 1,271 women between ages 18 and 49 years
at shopping malls and a flea market in El Paso, Texas, from May to July 2006. Eligible
women were given a checklist of contraindications to OC use, which was based on the
WHO MEC and a previously validated instrument [10], and asked to mark whether they had
any of the conditions listed. After completing the checklist, women were screened for these
same conditions by a nurse practitioner who was not aware of the participants selfscreening assessment. If the nurse practitioner was unsure or felt a woman needed further
evaluation regarding a specific condition, she was classified as contraindicated. The
questions used in each of these assessments are presented in Table 1. Women provided
verbal consent to participate in the study and received a $5$10 gift card to use at the
shopping mall or flea market following completion of the interview.

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In the second BCAS sub-study (the Prospective Study of OC Users), we recruited 1,046 El
Paso resident women between ages 18 and 44 years who either obtained their OCs at US
family planning clinics (n=532) or OTC from pharmacies in Mexico (n=514). In the baseline
interview, which was conducted between December 2006 and February 2008, bilingual
(English/Spanish) female interviewers read participants a list of medical conditions
considered contraindications to OC use and asked women to report if they currently have or
ever had the conditions. We assessed category 3 and category 4 contraindications according
to the WHO Medical Eligibility Criteria (MEC) 3rd edition, as the US MEC had not yet been
released [6,9,12]. This sub-study did not include screening by a clinician. Women who
reported any contraindication to OCs were referred to a health care provider. We also asked
women to report the specific brand of pill they were using and provided a pictorial guide to
assist them in identifying their brand. Prior to completing the baseline interview, women
provided written informed consent; they also received a $20 gift card for their participation.
Both sub-studies were approved by the Institutional Review Boards at the University of
Texas at Austin and University of Texas El Paso.

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In our analysis of both sub-studies, we focus on just those conditions that are considered
category 3 or 4 contraindications to initiation of POPs: history of or current breast cancer,
liver disease (i.e., severe cirrhosis) or liver tumors (hepatocellular adenoma or hepatoma),
and use of medications to treat seizures or tuberculosis (i.e., phenytoin, carbamazepine,
barbiturates, primidone, topiramate, oxcarbazepine, or rifampicin). We did not ask women
about whether they had systemic lupus erythematosus (SLE) with positive or unknown
antiphospholipid antibodies, malabsorptive bariatric surgery or used ritonavir-boosted
protease inhibitors or rifabutin, as these conditions were not included as contraindications to
POP use in the WHO MEC [12]. Women who were missing information on any of the POP
contraindications were excluded from analysis. Only four women were missing this
information in the Self-Screening Study, yielding a final sample of 1,267 women for this
analysis. None of the 1,046 participants in the Prospective Study were missing this
information.
In the Self-Screening Study, we computed the frequency of each self-reported
contraindication, as well as the frequency as assessed by the nurse practitioner. We also
assessed the sensitivity, specificity, positive and negative predictive values for report of any
contraindication in the checklist, using the nurse practitioners assessment as the gold

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standard. We calculated the 95% confidence intervals for these measures using the efficient
score method [13]. In the Prospective Study, we computed the frequency of each
contraindication to POPs and report of any contraindication by womens source of OCs at
baseline (clinic versus OTC). The statistical significance of differences in the proportions of
clinic and OTC users with any contraindication to POPs was determined using Fishers
exact test. We also examined the frequency of contraindications among women who were
using POPs at the time of the baseline assessment. All analyses were conducted using Stata
10.0 (Stata Corp., College Station, TX).

3. Results
3.1. Self-Screening Study
Of the 1,267 women included in this analysis, few reported having contraindications to
POPs (Table 2). Taking medications for tuberculosis or seizures was the most frequently
identified contraindication in both womens self-report and the provider assessment,
followed by history of liver disease and breast cancer. Overall, 1.7% (95% CI: 1.22.6%) of
women self-reported at least one contraindication to POPs, and a similar percentage of
women with contraindications were identified in the provider assessment (1.6%; 95% CI:
1.02.4%).

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Only five women (0.4%) failed to identify a contraindication to POPs when in fact the nurse
practitioner determined they had one; conversely, seven women (0.6%) indicated on the
checklist that they had a contraindication to POPs when they did not have a true
contraindication (Table 3). The sensitivity of the checklist for identifying women with at
least one contraindication to POPs was 75.0% (95% CI: 50.690.4%), while the specificity
was 99.4% (95% CI: 98.899.7%). The positive and negative predictive values for the
checklist in this sample were 68.2% (95% CI: 45.185.3%) and 99.6% (95% CI: 99.0
99.8%), respectively.
3.2. Prospective study of OC users
Among the 1,046 women currently using OCs, few reported conditions considered to be
contraindications to POPs, all of which are also contraindications to COCs (Table 4). In
total, 0.6% (95% CI: 0.31.2%) of women reported that they had at least one
contraindication. The prevalence of contraindications was slightly higher among OTC users
(1.0%) compared to clinic users (0.2%), but the prevalence of contraindications was not
significantly different for these two groups (p=0.118).

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Only 17 women (1.6% of the total sample) were using POPs at the time of the survey; seven
of these women obtained their method OTC in Mexico. None of the POP users reported
having any of the assessed contraindications (results not shown).

4. Discussion
We found that the prevalence of contraindications to POPs was very low both among a
sample from the general population and among current OC users in El Paso. We had
previously reported that the prevalence of COC contraindications was surprisingly high in
this population, possibly due to limited access to medical screening services [8,9]. The fact
that the prevalence of POP contraindications was so low here, and similar for individual
conditions reported in prior studies, likely reflects the rarity of these conditions among
reproductive aged women [7,10]. We also found that POP contraindications were rare
among women who obtained OCs OTC in Mexico and were absent among current POP
users.

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Women were able to accurately use the checklist to identify POP contraindications. In fact,
the specificity and negative predictive value of the checklist to diagnose POP
contraindications were significantly higher than these measures of the checklists ability to
diagnose COC contraindications [8]. The high negative predictive value of the selfscreening checklist (99.6%) indicates that it would be very unlikely for a woman to truly
have a POP contraindication after screening negative with the checklist.

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Even in the case of a missed true contraindication, the risk of serious harm is lower with
POPs compared to COCs. Women with contraindications such as hypertension, migraine
with aura and smoking at age 35 or older who use COCs are at higher risk of stroke, acute
myocardial infarction and peripheral arterial disease [6]. The above conditions are not
contraindications to POPs [6], and therefore, women would not be at risk for such adverse
cardiovascular events as a result of POP use. Moreover, we found that the most common
POP contraindication identified by a clinician was the use of certain medications for
tuberculosis or seizures, occurring among 0.9% of the sample in the Self-Screening Study.
Use of these medications reduces the effectiveness of POPs but does not otherwise harm
users [6]. And while contraindicated use among women with severe liver disease or breast
cancer may exacerbate these conditions, they are rare and usually known to the potential
user. It is also important to consider the risk of contraindicated use of OCseither COCs of
POPscompared to the risks of unintended pregnancy for someone with the same medical
conditions. Many of the contraindicated conditions, such as hypertension, liver disease or
breast cancer, would also be exacerbated by pregnancy.
In the Prospective Study, only about 2% of the sample was using POPs, while the remainder
was using COCs. Although there are no recent reports on the proportion of OC users in the
US that take POPs, it is likely similarly low nationwide. It is unclear why the use of POPs is
so uncommon. There may be a perception among providers and women that POPs are less
effective. However, a recent Cochrane review [14] found that the published evidence was
insufficient to draw conclusions about the relative efficacy of the two formulations and
recommended more research in this area. As a reflection of this lack of evidence,
contraceptive labeling reports the efficacy of oral contraceptives together without
differentiating between COCs and POPs [15]. In addition, current recommendations for
POPs, which suggest that backup contraception must be used if a pill is taken more than 3 h
later than the scheduled time, may contribute to a perception, at least among providers, that
the POP regimen is less convenient than COCs [16]. Yet these recommendations are not
based on firm evidence [17]. And while irregular menstrual bleeding is common with POPs,
there is no evidence that it is more frequent than with COCs [14,18].

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Another factor contributing to the low use of POPs may be related to marketing. Currently,
all POPs marketed in the US contain the same formulation of norethindrone. While
formulations containing levonorgestrel and desogestrel are available in other countries, there
has been no move to register these products in the US. It may be that pharmaceutical
companies see the POP market as narrowly limited to breastfeeding mothers and women
with contraindications to COCs. A POP formulation containing desogestrel 75 mcg has
become very popular in some European countries. In a randomized controlled trial of 989
women observed over one year, desogestrel 75 mcg had a lower pregnancy rate than
levonorgestrel 30 mcg, although the difference was not significant (Pearl index 0.14 (95%
CI: 0.0030.766) vs. 1.17 (95% CI: 0.2403.406)) [19]. Desogestrel 75 mcg appears to
prevent ovulation better than levonorgestrel 30 mcg [20,21]. This analysis has several
limitations. We likely overestimated POP contraindications among women in the
Prospective Study of OC Users, since they were not evaluated by a clinician to further
classify reports of liver disease and discard those that are not contraindications (such as a
history of hepatitis, mild cirrhosis and benign liver tumors). On the other hand, we did not

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screen for several new contraindications to POPs that were added to the US MEC in 2010,
such as history of SLE with positive or unknown antiphospholipid antibodies, malabsorptive
bariatric surgery or use of ritonavir-boosted protease inhibitors or rifabutin. We do not know
how common these conditions are in these populations, although we suspect they are rare. In
addition, our two sub-studies used convenience samples, which may limit the
generalizability of our findings.
Given the very low prevalence of contraindications to POPs, it may be that this formulation
would be the best choice for the first OTC oral contraceptive in the US. Not only are POP
contraindications rare, but women appear to be able to accurately identify them using a
simple checklist without the aid of a clinician. While the launch of an OTC POP would be
an opportunity to re-brand this formulation, it remains to be seen whether there would be
significant uptake of a new POP. More rigorous research is needed on the efficacy and side
effects of POPs compared to COCs, as well as the effectiveness and acceptability of POPs
provided in an OTC setting.

Acknowledgments
The study was funded by a grant from the Eunice Kennedy Shriver National Institute of Child Health and Human
Development (R01HD047816). We wish to thank the late Charlotte Ellertson for her contribution to the
development of this project and Michele G. Shedlin for her comments on an earlier version of the manuscript.

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References

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16. Freeman S, Shulman LP. Considerations for the use of progestin-only contraceptives. J Am Acad
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Table 1

Assessment of contraindications to progestin-only pills in the Self-Screening Study

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Self-assessment

Provider screening

Do you take medicine for seizures or

tuberculosis (TB)?

Do you take any of the following medications currently: Rifampicin (Rifampin) or

anticonvulsants such as phenytoin (Dilantin), carbemazepine (Tegretol), barbituates,
primidone (Myidone or Mysoline), topiramate (Topamax) or oxcarbazepine (Trileptal)?

Do you have liver disease or have you had

liver cancer?

Do you currently have liver disease (active viral hepatitis or cirrhosis) or have you had liver
cancer in the past?

Have you had breast cancer?

Do you currently have breast cancer or have you had breast cancer in the past?

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TB = Tuberculosis

4
22

Any contraindication

Current liver disease or history of liver cancer

History of or current breast cancer

Current use of medications for TB or seizures

(1.7)

(0.3)

(0.7)

(0.7)

(%)

Self-assessment

20

11

(1.6)

(0.3)

(0.4)

(0.9)

(%)

Provider screening

15

(75.0)

(100.0)

(80.0)

(63.6)

(%)

Correctly identified

Frequency of contraindications to progestin-only pills according to self-assessment and provider screening in the Self-Screening Study(n=1,267)

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Table 2
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(1.6, 1.02.4)

20

Total

C.I. = Confidence Interval

(0.4, 0.20.9)

(1.2, 0.71.9)

15

No contraindications

Contraindicated to POPs

Self-assessment

Contraindicated to POPs
n (%, 95% C.I.)

1,247

1,240

(98.4, 97.699.0)

(97.9, 96.998.5)

(0.6, 0.31.1)

No contraindications
n (%, 95% C.I.)

Provider screening

1,267

1,245

22

(100.0)

(98.3, 97.498.9)

(1.7, 1.22.6)

Total
n (%, 95% C.I.)

Accuracy of self-assessment compared to provider screening for contraindications to progestin-only pills(POPs) in the Self-Screening Study

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Table 3
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Table 4

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Frequency of contraindications to progestin-only pills according to source of pills at baseline in the

Prospective Study of OC Users (n=1,046)
Clinic

OTC

(%)

(%)

Current use of medications for TB or seizure

(0.2)

(0.2)

Current liver disease or history of liver cancer

(0.0)

(0.6)

History of or current breast cancer

(0.0)

(0.2)

Any contraindication

(0.2)

(1.0)

TB = Tuberculosis

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